Identification of N-methyl-D-aspartate receptor antagonists using the rat postnatal mixed cortical and hippocampal neurons

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00558330" target="_blank" >RIV/61388963:_____/22:00558330 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.ejphar.2022.175056" target="_blank" >https://doi.org/10.1016/j.ejphar.2022.175056</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2022.175056" target="_blank" >10.1016/j.ejphar.2022.175056</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of N-methyl-D-aspartate receptor antagonists using the rat postnatal mixed cortical and hippocampal neurons

Popis výsledku v původním jazyce

The goal of this study was to evaluate mixed cortical and hippocampal primary rat postnatal neuronal culture as in vitro tool for identification of N-methyl-D-aspartate receptor (NMDAR) antagonists and to find out, whether this model is comparable with other commonly used primary rat neuronal models differing in their origin (pure cortical vs. mixed cortical and hippocampal) and differentiation state (embryonal vs. postnatal). Induced pluripotent stem cell (iPSC) – derived human glutamatergic neurons have been included in this study as well. First, the cultures were characterized by their neuron/astrocyte composition, the mRNA expression of NR2B/NR2A NMDAR subunit ratios, and the expression of glutamate transporters (GLT1, GLAST). Then, selected endogenous steroids and synthetic neuroactive steroids that have been previously identified as negative allosteric modulators of recombinant GluN1/GluN2B NMDA receptors, were evaluated for their ability to prevent an NMDA or glutamate-induced Ca2+ influx (acute effect) and excitotoxicity over 24 h. Though the neuroprotective potential against excitotoxic stimuli varied among the models studied, postnatal mixed cortical and hippocampal culture proved to be a convenient and robust tool for NMDAR antagonist screening. The most widely used embryonal (E18) cultures offered higher cell yields but at the expense of a higher sensitivity to compounds’ cytotoxicity. iPSC-derived neurons were not found to be superior to rat cultures for screening purposes.

Název v anglickém jazyce

Identification of N-methyl-D-aspartate receptor antagonists using the rat postnatal mixed cortical and hippocampal neurons

Popis výsledku anglicky

The goal of this study was to evaluate mixed cortical and hippocampal primary rat postnatal neuronal culture as in vitro tool for identification of N-methyl-D-aspartate receptor (NMDAR) antagonists and to find out, whether this model is comparable with other commonly used primary rat neuronal models differing in their origin (pure cortical vs. mixed cortical and hippocampal) and differentiation state (embryonal vs. postnatal). Induced pluripotent stem cell (iPSC) – derived human glutamatergic neurons have been included in this study as well. First, the cultures were characterized by their neuron/astrocyte composition, the mRNA expression of NR2B/NR2A NMDAR subunit ratios, and the expression of glutamate transporters (GLT1, GLAST). Then, selected endogenous steroids and synthetic neuroactive steroids that have been previously identified as negative allosteric modulators of recombinant GluN1/GluN2B NMDA receptors, were evaluated for their ability to prevent an NMDA or glutamate-induced Ca2+ influx (acute effect) and excitotoxicity over 24 h. Though the neuroprotective potential against excitotoxic stimuli varied among the models studied, postnatal mixed cortical and hippocampal culture proved to be a convenient and robust tool for NMDAR antagonist screening. The most widely used embryonal (E18) cultures offered higher cell yields but at the expense of a higher sensitivity to compounds’ cytotoxicity. iPSC-derived neurons were not found to be superior to rat cultures for screening purposes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/TN01000013" target="_blank" >TN01000013: Personalizovaná medicína - diagnostika a terapie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Pharmacology

ISSN

0014-2999

e-ISSN

1879-0712

Svazek periodika

927

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

175056

Kód UT WoS článku

000809747800002

EID výsledku v databázi Scopus

2-s2.0-85131435177